Children and adolescents in the United States continue to eat more and exercise less than their parents did a generation ago;this combination of overnutrition and inactivity is partly to blame for an epidemic of obesity that threatens to shorten life expectancy of young people. Many of the adverse sequelae of obesity are mediated by insulin resistance. Understanding how to reverse obesity-associated insulin resistance in this vulnerable population is of critical public health importance. The proposed study is a randomized controlled trial to evaluate the impact of a supervised in-home 8-week exercise training intervention on insulin resistance in overweight children and adolescents, and to explore the mechanisms by which fitness-related amelioration of insulin resistance may occur. Specifically, we hypothesize that exercise will produce alterations in skeletal muscle physiology that will improve insulin sensitivity. The amount of lean mass, mitochondrial function, and intramyocellular lipid content are candidate modulators of insulin resistance at the level of the skeletal muscle that may be affected by exercise;we will investigate the potential contribution of each of these to exercise- related changes in insulin sensitivity. Finally, to support and extend our findings, we propose to simultaneously measure the concentrations of many metabolites (amino acids, sugars, low molecular weight lipids). We hope to identify other biological pathways modifiable by exercise and associated with better insulin sensitivity that can be the focus of future work. A better understanding of how exercise may ameliorate insulin resistance could shed light on pathogenesis of this condition and lead to more effective exercise prescriptions for patients. PUBLIC HEALTH RELEVANCE: Children and adolescents in the United States continue to eat more and exercise less than their parents did a generation ago;this combination of excess nutrition and inactivity is partly to blame for an epidemic of obesity that threatens to shorten life expectancy of young people. We propose a study to evaluate whether exercise can reverse some of the harmful effects of obesity in this important population, and if so, how it might work. We hope that a better understanding of how exercise helps will lead to insights into obesity and its consequences in children and adolescents, as well as more effective exercise prescriptions for our pediatric patients.